Novel Roles for Arginase in Cell Survival, Regeneration, and Translation in the Central Nervous System

In this review the current knowledge about the arginine-degrading enzyme arginase and its unexpected roles in survival and regeneration in the central nervous system will be discussed. Recent data suggest the neuroprotective effects of extracellularly applied arginase can be attributed to an activation of the endoplasmic reticulum stress response with a consequent change of the pro-survival gene expression profile. However, the activation of neural regeneration pathways caused by an upregulation of endogenous arginase I is mediated by polyamines, a group of arginase downstream products with widespread biological effects. In light of these new discoveries, there is heightened interest in the regulation of arginase I gene expression within the central nervous system. A number of transcription factors such as Sp1, C/EBP (CCATT/enhancer-binding protein), and CREB seem to be involved in the transcriptional control of arginase I and may contribute to the complex expression pattern of arginase I in distinct brain regions and during development. Beyond molecular mechanisms, this review will also include relevant clinical findings in patients with neurodegenerative diseases.